THE BIOLOGIC EFFECTS OF T3 AND T4; THEIR RELATIVE POTENCY AND THE SOURCE OF MOST CIRCULATING T3
What are the biologic effects of T3 and T4
Thyroid hormone exerts effects on virtually all tissues of the body either directly or indirectly
1. Thyroid hormone increase basal metabolic rate and heat production
Thyroid hormone increases basal metabolic rate of the body. It increases O2 composition in most tissues. Furthermore, it increases energy expenditure under resting conditions.
Closely related to thyroid hormones effect on BMR is its thermogenic (i.e. heat-producing effect). Increased metabolic activity results in increased heat production.
2. Thyroid hormone displays sympathomimetic effect
A sympathomimetic effect is any action similar to the one produced by the sympathetic nervous system.
Thyroid hormone amplifies target cell responsiveness to catecholamines (epinephrine and norepinephrine), the two chemical messengers utilized by the sympathetic nervous system and its hormonal reinforcement from the adrenal medulla.
Thus, thyroid hormone displays permissiveness with norepinephrine and epinephrine. This permissiveness is accompanied by causing a proliferation of specific catecholamine target receptors.
With permissiveness, one hormone must be available in sufficient amounts for the full manifestation of another hormone’s effect. In this case, thyroid hormone by promoting a target cells’ responsiveness to epinephrine permits epinephrine to exert its full effect.
Thyroid hormone increases the number of receptors on epinephrine’s target cells increasing the effectiveness of epinephrine. In the absence of thyroid hormone, epinephrine is only marginally effective.
Because of this permissiveness, many of the symptoms observed in people who suffer hypersecretion of thyroid hormone are similar to those that accompany sympathetic nervous system activation.
3. Thyroid hormone increases heart rate and force of contraction
Through its effect of increasing the responsiveness of the heart to circulating catecholamine, thyroid hormone increases heart rate and force of contraction therefore, increasing cardiac output. Moreover, the heat load generated by the thermogenic effect of thyroid hormone causes peripheral vasodilation which serves to carry the extra heat to the body surface for elimination to the environment.
4. Thyroid hormone is required for normal growth and the development of the central nervous system.
Thyroid hormone is necessary for normal growth because of its effect on growth hormone.
a. Thyroid hormone stimulates growth hormone secretion.
b. It enhances the effects of GH (or somatomedins) on the synthesis of new structural proteins. In children, thyroid hormones are necessary for full expression of GH, which implies they are essential for normal growth and development. Little wonder children who suffer thyroid hormone deficiency have retarded growth.
c. Thyroid hormone promotes the effect of GH on skeletal growth.
Thyroid hormone is essential for normal CNS development; this explains why children who suffer hypothyroidism from birth develop a condition called cretinism. Cretinism is marked by dwarfism (stunted growth) and mental retardation.
Thyroid deficient children typically have stunted growth, which can be corrected by thyroid replacement therapy. However, excess thyroid hormone, unlike excess growth hormone, does not produce excessive growth.
Between T4 and T3, which is more potent?
Most thyroid hormone in the plasma is in the form of T4. Actually about 90% of the secretory products released from the thyroid gland is in the T4 form. Consequently, for years, it was apparently believed that T4 was the active hormone. However, we now know that T3 is about four times more potent in its biological effects. Accordingly, T3 is the active hormone in target cells.
What is the source of most circulating T3
Most of the secreted T4 is converted to T3 (i.e. activated) by being stripped of one of its iodines outside of the thyroid gland. This occurs mainly in the liver and kidneys. A large portion of the T4 is activated to T3 in the target cells where they exert biological actions. Thus, most circulating T3 do not come from the thyroid gland but from peripheral activation.
About 85% of circulating T3 is derived from T4 that has been stripped in the peripheral tissues.
Thus, at cellular level, T3 is the more potent and/or the major biologically active form of the thyroid hormones, although the thyroid gland secretes mostly T4.
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